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Endothelin Mechanism of Action |
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The synthesis of endothelin (ET) in vascular endothelial cells is complex, beginning with preproendothelin, a large precursor molecule. Preproendothelin is processed by furin-like proteases into biologically inactive big endothelins,1 and finally converted by ET-converting enzyme (ECE) to fully active ET.2 |
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Once released from the endothelium, ET exerts its effects through binding to two receptors, ETA and ETB. The consequences of binding differ according to the cell type on which the receptors are found.3 |
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REFERENCES |
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1. |
Kedzierski RM, Yanagisawa M. Endothelin system: the double-edged sword in health and disease. Annu Rev Pharmacol Toxicol. 2001;41:851–876. |
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2. |
Braunwald E, Zipes DP, Libby P, eds. Heart Disease. 2 vols. 6th ed. Philadelphia, PA: WB Saunders Co; 2001:1096.
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3. |
Kim NH, Rubin LJ. Endothelin in health and disease: endothelin receptor antagonists in the management of pulmonary artery hypertension. J Cardiovasc Pharmacol Ther. 2002;7:9–19. |
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4. |
Rae GA, Henriques MGMO. Endothelins in inflammation. In Said SI, ed. Proinflammatory and Antiinflammatory Peptides. New York: Marcel Dekker Inc; 1998:163–202. |
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5. |
Davie N, Haleen SJ, Upton PD, et al. ET(A) and ET(B) receptors modulate the proliferation of human pulmonary artery smooth muscle cells. Am J Respir Crit Care Med. 2002;165:398–405. |
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6. |
Piacentini L, Gray M, Honbo NY, Chentoufi J, Bergman M, Karliner JS. Endothelin-1 stimulates cardiac fibroblast proliferation through activation of protein kinase C. J Mol Cell Cardiol. 2000;32:565–576. |
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7. |
Katwa LC, Guarda E, Weber KT. Endothelin receptors in cultured adult rat cardiac fibroblasts. Cardiovasc Res. 1993;27:2125–2129. |
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